Transporters

Question 1

example of efflux transporter

Answer 1

P-glycoprotein

Question 2

uptake transporters (2)

Answer 2

• OATP
• PEPT1

Question 3

uptake transporters

• OATP (organic ___ trasporting protein)
• PEPT1 (____ transporter 1)

Answer 3

• anionic
• peptide

Question 4

P-glycoprotein

• Efflux transporter affecting ___ of drugs
• leads to ___ to certain drugs
• also called ___

Answer 4

• permeability
• resisitance
• MDR1

Question 5

T or F: Inhibition of P-gp in cancer cell is expected to improve anticancer drug efficacy by increasing intracellular drug concentrations

Answer 5

True

Question 6

P-gp tissue distribution

P-gp is expressed on the ___ side

Answer 6

apical

Question 7

BBB

• brain capillaries have ___ junctions, not ___.
• brain capillaries are surrounded by ___.
• ___ mediated transport used

Answer 7

• tight, pores
• astrocyte processes
• carrier

Question 8

P-glycoprotein (P-gp) inhibitors

Most P-gp inhibitors are also substrates of P-gp and capable of ___ inhibiting P-gp function.

Answer 8

competitively

Question 9

T or F: Inhibition of P-gp in brain is expected to increase the penetration of P-gp substrates into brain

Answer 9

True

Question 10

T or F: HIV-associated Neurocognitive Disorders occurs when HIV enters the nervous system and impacts
the health of nerve cell. Combining HIV protease inhibitors (P-gp substrates) with P-gp inhibitors will likely increase
brain distribution of anti-HIV drugs.

Answer 10

True

Question 11

• portal vein to central vein (traveling ___)
• Bile canaliculus to bile duct (traveling ___)

Answer 11

• in
• outward

Question 12

P-gp in liver

• Expressed at the bile ___ membrane of the liver
• P-gp substrates are subject to ___ excretion

Answer 12

• canalicular
• biliary

Question 13

T or F: Combining paclitaxel with a P-gp inhibitor will likely decrease biliary excretion of paclitaxel.

Answer 13

true

Question 14

T or F: Biliary excretion of paclitaxel is its major elimination route. Combining paclitaxel with a P-gp
inhibitor will likely decrease paclitaxel elimination from the body and increase systemic drug concentration

Answer 14

true

Question 15

T or F: P-gp inhibitors will likely increase the passage of P-gp substrates across placenta, leading to increased fetal drug levels

Answer 15

true

Question 16

OATP Superfamily

• > ___ members with at least ___ OATPs expressed in humans
• type of ___ transporters
• Substrates are ___ compounds such as ___, ___, and ___
• Xenobiotics: ___ and ___

Answer 16

• 300, 11
• uptake
• endogenous, bilirubin, bile salts, and steroid hormone
• fexofenadine, statin

Question 17

T or F: OATP1B1 inhibition will likely decrease the intrahepatic concentration OATP1B1 substrates

Answer 17

true

Question 18

Statins and OATP1B1

• statins inhibit ___ reductase in the ___
• substrate of ___
• life threatening side effect: ___
• Risks were higher in patients using fibrates, mainly ___ (an inhibitor), and in patients using the highest dose of cerivastatin

cerivastatin was discontinued in 2001

Answer 18

• HMG-CoA
• OATP1B1
• rhabdomyolysis
• gemfibrozil

Question 19

Statins and OATP1B1

When OATP1B1 is inhibited
* statin hepatic concentration ___
* statin plasma concentration ___
* statin myopathy ___
* ___ efficacy
* ___ side effects

Answer 19

• decreased
• increased
• increased
• lower
• increased

Question 20

OATP1B1 genetic polymorphisms and statins

the ___ genotype is more likely to have side effects

Answer 20

CC

Question 21

___ juice inhibits OATP

Answer 21

Grapefruit

Question 22

PEPT1 (peptide transporter 1)

• A peptide transporter in the ___
• uptake transporter
• substrates: ___, ___, and ___
• utilized to improve ___ absorption of drugs

Answer 22

• small intestine
• dipeptides, tripeptides, and β-Lactam
• oral

Question 23

• Acyclovir absorption ___
• Valacyclovir (prodrug) absorption ___

Answer 23

• 20%
• complete

Question 24

When administered at the same dose,
___ leads to higher systemic
exposure to ___

Answer 24

• valacyclovir
• acyclovir

Question 25

Which of the following is NOT the expected biological consequence of a P-gp substrate drug when it is co-administered with a P-gp inhibitor?

• Increased brain distribution
• Increased biliary excretion
• Increased intestinal absorption
• Increased drug transfer to fetus

Answer 25

Increased biliary excretion

Question 26

Which one of the following transporters is responsible for increased absorption of valacyclovir as compared to acyclovir?

• P-gp
• OATP1B1
• PEPT1
• OCT1

Answer 26

PEPT1

Question 27

Which one of the following transporters is responsible for hepatic uptake of statins?
* P-gp
* OATP1B1
* PEPT1
* OCT1

Answer 27

OATP1B1

Question 28

Genetic polymorphisms of OATP1B1 that are associated with nonfunctional transporter activity would lead to

• Increased hepatotoxicity of statins
• Decreased efficacy of statins
• Decreased myopathy of statins
• None of the above

Answer 28

Decreased efficacy of statins